Convergence in the piriform cortex

How are the responses to distinct chemical features integrated to form an olfactory perceptual object? In this issue of Neuron, Davison and Ehlers show that individual piriform cortex neurons receive convergent input from up to 10% of main olfactory bulb glomeruli and are activated by specific spatial patterns of coactive glomeruli.     

Long-term potentiation in the piriform cortex is blocked by lead

Summary 1. Long-term potentiation (LTP) is a prolonged increase in synaptic efficacy that is triggered by a brief tetanic stimulation at certain central synapses. LTP is one of the best available model systems available to the neurophysiologist of neuronal plasticity such as that underlying learning and memory.2. We have studied the susceptibility of LTP to blockade by lead as a test of the hypothesis that the negative effect of lead on intelligence in children may result from interference with this process. LTP was studied in slices of rat piriform cortex. At this site, as in many other central synapses, LTP requires activation of postsynapticN-methyl-d-aspartate (NMDA) receptors, and we investigated whether lead actions, if any, were mediated via effects on NMDA-activation ion channels or, alternatively, at voltage-activated calcium channels.3. We find that lead blocks LTP at low micromolar concentrations. However, concentrations of lead that totally block LTP had no apparent effect on either NMDA-activated responses or presynaptic calcium channels, as monitored by transmitter release from presynaptic terminals.4. While the mechanism of lead blockade of LTP remains to be determined, these observations are consistent with the hypothesis that the cognitive effects of lead neurotoxicity may result from effects on LTP.     

Receptive fields in the rat piriform cortex.

Current models of odor discrimination in mammals involve molecular feature detection by a large family of diverse olfactory receptors, refinement of molecular feature extraction through precise projections of olfactory receptor neurons to the olfactory bulb to form an odor-specific spatial map of molecular features across glomerular layer, and synthesis of these features into odor objects within the piriform cortex. This review describes our recent work on odor and spatial receptive fields within the anterior piriform cortex and compares these fields with receptive fields of their primary afferent, olfactory bulb mitral/tufted cells. The results suggest that receptive fields in the piriform cortex are ensemble in nature, highly dynamic, and may contribute to odor discrimination and odor memory.     

Acetylcholine and associative memory in the piriform cortex

The significance of cholinergic modulation for associative memory performance in the piriform cortex was examined in a study combining cellular neurophysiology in brain slices with realistic biophysical network simulations. Three different physiological effects of acetylcholine were identified at the single-cell level: suppression of neuronal adaptation, suppression of synaptic transmission in the intrinsic fibers layer, and activity-dependent increase in synaptic strength. Biophysical simulations show how these three effects are joined together to enhance learning and recall performance of the cortical network. Furthermore, our data suggest that activity-dependent synaptic decay during learning is a crucial factor in determining learning capability of the cortical network. Accordingly, it is predicted that acetylcholine should also enhance long-term depression in the piriform cortex.     

N-methyl-d-aspartate andl-aspartate activate distinct receptors in piriform cortex

The effects of ionophoretically applied N-methyl-DL-aspartate (NMDA) and aspartate on identified pyramidal neurons in rat piriform cortex were examined in isolated, submerged, and perfused brain slices. NMDA was more potent than aspartate in eliciting neuronal discharge. Perfusion of the acidic amino acid antagonists, DL-2-amino-5-phosphonovalerate (APV), 10(-6) or 10(-5) M, DL-2-amino-7-phosphonoheptanoate (APH), 10(-5) M, and gamma-D-glutamylglycine (gamma DGG), 10(-5) M, selectively blocked the response to NMDA without effect on the response to aspartate. At higher concentrations which blocked responses to both NMDA and aspartate, gamma DGG blocked kainate responses and depressed glutamate and quisqualate responses. These results suggest that in piriform neurons NMDA and aspartate act at distinct receptor sites, not a common receptor site, and that both of these sites are distinct from those that mediate responses to glutamate, quisqualate, and kainate.     

Optical recording of the in vivo piriform cortex responses to electrical stimulation of the lateral olfactory tract in the rat

Using a voltage-sensitive styryl dye, optical recordings ofthe piriform cortex responses to bipolar electrical stimulationsof the rat lateral olfactory tract (LOT) were taken. Surgicalprocedures were performed on Wistar SPF male rats anaesthetizedwith equithesine. Anaesthesia was continued during the recording.In addition the animals were curarized and artificially ventilated.Piriform cortex was stained with RH795. Cortical fluorescencewas recorded with a 124-element photodiode array using epi-illuminationwhile electrical stimulations were delivered to the LOT. Mappingof the piriform activity indicated a very large overlap of therecorded responses. Nevertheless, some differences in locationof recorded responses were observed and seemed to correlatewith the location of the stimulation electrode on the LOT. Theresults are discussed in relation to the anatomy and histologyof the olfactory bulb projections to the piriform cortex.     

Recurrent circuitry dynamically shapes the activation of piriform cortex

In the piriform cortex, individual odorants activate a unique ensemble of neurons that are distributed without discernable spatial order. Piriform neurons receive convergent excitatory inputs from random collections of olfactory bulb glomeruli. Pyramidal cells also make extensive recurrent connections with other excitatory and inhibitory neurons. We introduced channelrhodopsin into the piriform cortex to characterize these intrinsic circuits and to examine their contribution to activity driven by afferent bulbar inputs. We demonstrated that individual pyramidal cells are sparsely interconnected by thousands of excitatory synaptic connections that extend, largely undiminished, across the piriform cortex, forming a large excitatory network that can dominate the bulbar input. Pyramidal cells also activate inhibitory interneurons that mediate strong, local feedback inhibition that scales with excitation. This recurrent network can enhance or suppress bulbar input, depending on whether the input arrives before or after the cortex is activated. This circuitry may shape the ensembles of piriform cells that encode odorant identity.     

Neuromodulation and the functional dynamics of piriform cortex.

Acetylcholine and norepinephrine have a number of effects at the cellular level in the piriform cortex. Acetylcholine causes a depolarization of the membrane potential of pyramidal cells and interneurons, and suppresses the action potential frequency accommodation of pyramidal cells. Acetylcholine also has strong effects on synaptic transmission, suppressing both excitatory and inhibitory synaptic transmission. At the same time as it suppresses synaptic transmission, acetylcholine enhances synaptic modification, as demonstrated by experiments showing enhancement of long-term potentiation. Norepinephrine has similar effects. In this review, we discuss some of these different cellular effects and provide functional proposals for these individual effects in the context of the putative associative memory function of this structure.     

Olfactory predictive codes and stimulus templates in piriform cortex

Neuroscientific models of sensory perception suggest that the brain utilizes predictive codes in advance of a stimulus encounter, enabling organisms to infer forthcoming sensory events. However, it is poorly understood how such mechanisms are implemented in the olfactory system. Combining high-resolution functional magnetic resonance imaging with multivariate (pattern-based) analyses, we examined the spatiotemporal evolution of odor perception in the human brain during an olfactory search task. Ensemble activity patterns in anterior piriform cortex (APC) and orbitofrontal cortex (OFC) reflected the attended odor target both before and after stimulus onset. In contrast, prestimulus ensemble representations of the odor target in posterior piriform cortex (PPC) gave way to poststimulus representations of the odor itself. Critically, the robustness of target-related patterns in PPC predicted subsequent behavioral performance. Our findings directly show that the brain generates predictive templates or "search images" in PPC, with physical correspondence to odor-specific pattern representations, to augment olfactory perception.     

Long-term modifications in the strength of excitatory associative inputs in the piriform cortex

Afferent olfactory information, in vivo and in vitro, can be rapidly adapted to through a metabotropic glutamate receptor (mGluR)-mediated attenuation of synaptic strength. Specific cellular and synaptic mechanisms underlying olfactory learning and habituation at the cortical level remain unclear. Through whole-cell recording, excitatory postsynaptic currents (EPSCs) were obtained from piriform cortex (PC) principal cells. Using a coincidental, pre- and postsynaptic stimulation protocol, long-term depression (LTD) in synaptic strength was induced at associative, excitatory synapses onto layer II pyramidal neurons of the mouse (P15-27) PC. LTD was mimicked and occluded by mGluR agonists and blocked by nonselective mGluR antagonist (RS)-alpha-methyl-4-sulfonophenylglycine (MSPG) but not by N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Analysis of the paired-pulse ratio, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA current ratio, and spontaneous EPSCs indicate that electrically induced LTD was mediated predominantly by postsynaptic mechanisms. Additionally, presynaptic mGluRs were involved in agonist-mediated synaptic depression. Immunohistochemical analysis supports the presence of multiple subclasses of mGluRs throughout the PC, with large concentrations of several receptors present in layer II. These observations provide further evidence of activity-dependent, long-term modification of associative inputs and its underlying mechanisms. Cortical adaptation at associative synapses provides an additional link between cortical olfactory processing and subcortical centers that influence behavior.     

Frequency analysis of motor responses evoked in unanesthetized cats by stimulation of the motor cortex

Frequency characteristics of motor responses evoked by stimulation of the motor cortex by amplitude- and frequency-modulated stimulus sequences were investigated in chronic experiments on unanesthetized cats. The variable component of evoked muscular contraction was studied. Frequency characteristic curves were plotted by the harmonic linearization method. Transformation of controlling signals in the motor system was shown to take place by low-frequency filtration and to be characterized by nonstationary, nonlinear, and frequency-dependent properties. Phase delay of the principal harmonic of the variable component of evoked muscular contraction was minimal at a frequency of 0.2 Hz and it varied in different experiments from 40 to 90°. The increase in the phase delay and decline of the amplitude-frequency characteristic curves were particularly marked if the frequency exceeded 1–2 Hz. The mean phase delay at a frequency of 5 Hz was about 108°; the mean slope of the amplitude characteristic curves in the 2–10 Hz region was –12 dB/decade. It is suggested that definite correlation between the dynamic properties of the motor system may be determined, in particular, by the adaptive properties of the spike discharge of neurons concerned in the transmission of motor command signals.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 6, pp. 571–579, November–December, 1980.     

Characterization and isolation of immature neurons of the adult mouse piriform cortex

Physiological studies indicate that the piriform or primary olfactory cortex of adult mammals exhibits a high degree of synaptic plasticity. Interestingly, a subpopulation of cells in the layer II of the adult piriform cortex expresses neurodevelopmental markers, such as the polysialylated form of neural cell adhesion molecule (PSA‐NCAM) or doublecortin (DCX). This study analyzes the nature, origin, and potential function of these poorly understood cells in mice. As previously described in rats, most of the PSA‐NCAM expressing cells in layer II could be morphologically classified as tangled cells and only a small proportion of larger cells could be considered semilunar‐pyramidal transitional neurons. Most were also immunoreactive for DCX, confirming their immature nature. In agreement with this, detection of PSA‐NCAM combined with that of different cell lineage‐specific antigens revealed that most PSA‐NCAM positive cells did not co‐express markers of glial cells or mature neurons. Their time of origin was evaluated by birthdating experiments with halogenated nucleosides performed at different developmental stages and in adulthood. We found that virtually all cells in this paleocortical region, including PSA‐NCAM‐positive cells, are born during fetal development. In addition, proliferation analyses in adult mice revealed that very few cells were cycling in layer II of the piriform cortex and that none of them was PSA‐NCAM‐positive. Moreover, we have established conditions to isolate and culture these immature neurons in the adult piriform cortex layer II. We find that although they can survive under certain conditions, they do not proliferate in vitro either. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 748–763, 2016     

Dissociable codes of odor quality and odorant structure in human piriform cortex

The relationship between odorant structure and odor quality has been a focus of olfactory research for 100 years, although no systematic correlations are yet apparent. Animal studies suggest that topographical representations of odorant structure in olfactory bulb form the perceptual basis of odor quality. Whether central olfactory regions are similarly organized is unclear. Using an olfactory version of fMRI cross-adaptation, we measured neural responses in primary olfactory (piriform) cortex as subjects smelled pairs of odorants systematically differing in quality and molecular functional group (as one critical attribute of odorant structure). Our results indicate a double dissociation in piriform cortex, whereby posterior regions encode quality (but not structure) and anterior regions encode structure (but not quality). The presence of structure-based codes suggests fidelity of sensory information arising from olfactory bulb. In turn, quality-based codes are independent of any simple structural configuration, implying that synthetic mechanisms may underlie our experience of smell.     

Development of dendritic spines in the piriform neurons of the cerebellar cortex in human prenatal ontogeny

The submicroscopic investigation on developmental peculiarities of the dendritic spines in the piriform neurons of the cerebellar cortex has been performed during the human prenatal ontogenesis. The process of morphogenesis of the spines of the tertiary dendrites in the piriform neurons is demonstrated to start rather early--on the 24th week of embryogenesis and goes through three successive stages: 1) formation of a long cytoplasmic processes deprived of any membranous specialization; 2) formation of the terminal spinal head, making synapses with parallel fibers of the cerebellar cortex; 3) definitive stage. A suggestion is made that differentiation processes of the spines depend on inductive influence of the parallel fibers of the cerebellar cortex.